In order to reduce their long-term risk of AIDS-defining illnesses, HIV-positive people who have low CD4 counts when they start treatment should focus on getting and keeping their viral load undetectable, according to a study published in the February 1 issue of The Journal of Infectious Diseases. Though people starting treatment for the first time who experience rapid CD4 gains face a lower risk of AIDS illness than those whose CD4s respond more slowly, this difference diminishes after six months provided that viral load remains undetectable.

Up to 30 percent of all people entering HIV care for the first time have CD4 counts below 200, and a significant percentage actually have CD4s under 100. This is a particular concern, as the lower a person’s CD4 counts at the time of starting treatment, the more likely he or she is to be a discordant responder—a very slow CD4 cell count recovery, despite an undetectable viral load—and the more likely the person is to have poor outcomes overall.

Studies on discordant responders are relatively sparse, however, and most have focused on the first six or 12 months following the start of treatment. For this reason, providers have differed in their care of patients whose CD4s don’t come up quickly after they start antiretroviral (ARV) therapy. While some providers make no treatment changes provided that HIV remains fully suppressed, others change or add new drugs in hopes of getting a better CD4 boost.

To determine the risk of disease progression in discordant responders and to better guide such treatment decisions, Alexander Zoufaly, MD, from the University Medical Center Hamburg-Eppendorf, in Hamburg, Germany, and his colleagues examined data from the German Clinical Surveillance of HIV Disease (ClinSurv) Cohort Study. From the 14,000 individuals in the cohort, Zoufaly’s team identified 1,318 patients who were starting treatment for the first time, whose CD4s were under 200 when they started treatment and who ultimately achieved and sustained viral loads under 50 copies.

Zoufaly and his colleagues broke the larger group down by the length of time it took for the participants to have a good CD4 increase. They defined those who had significant CD4 increases—defined as achieving and maintaining a CD4 count over 200—within the first six months as early responders, and all others as late responders. In all, 837 (64 percent) were early responders, and the remaining 481 (36 percent) were late responders. Among the late responders, however, 99 had persistently low CD4s beyond two years after starting treatment.

Over the course of the study 42 new AIDS-defining illnesses occurred. The incidence of these illnesses was highest during the first six months after people started treatment, and this was true regardless of whether a person was an early or late responder. The rate of new AIDS events, however, was more than three times higher among the late responders as the early responders.

Of note, however, the rate of new illnesses diminished by up to 65 percent per year in late responders and about 40 percent per year in early responders. By the second year after treatment was started, the number of new AIDS events was minuscule in both groups and the difference between new and late responders had essentially evened out.

The authors state that these data are encouraging: “In concert with these data, our results indicate that CD4 cell counts are of limited use as long-term surrogates for absolute AIDS risk as long as complete virological suppression is sustained.”

It should be noted that other negative health effects, including non-AIDS illnesses such as certain cancers, have been shown to disproportionately strike those with persistently lower CD4 counts. Moreover, as the study had so few new AIDS-defining events, it is possible that the actual risk may be higher in another study with larger numbers of events. Further research will likely be needed to confirm these results, but they are encouraging nevertheless.

“These data from a large multicenter cohort show that the risk to develop new AIDS-defining events is substantially reduced after the first six months of complete viral suppression, irrespective of the numeric indicators of immune reconstitution,” the authors write.

“This should further encourage physicians to define complete viral suppression as the primary goal for their patients who are receiving [ARVs], including those patients who start therapy in advanced stages of immune deficiency,” they conclude.